Objective      To study the role of carfilzomib (CFZ) in the amelioration of skeletal muscle consumption in cancer cachexia and its associated mechanism.        Methods      Cancer cachexia model was induced by injecting murine colon 26 adenocarcinoma cells into male BALB/c mice intraperitoneally. BALB/c mice were divided into 4 groups randomly

including a healthy control group (HC)

a CFZ prevention group (CP)

a CFZ treatment group (CT) and a cancer cachexia group (CC). At different time points

food intake

body weight and spontaneous activity were detected. Following administration of CFZ intraperitoneally twice a week to CP and CT groups on the days 5 and 12 after tumor cells injection

respectively

all mice were sacrificed on day 19. Mouse body

tumor entity and gastrocnemius muscle on the left side were accurately weighed and the volume of tumors were measured. The serum levels of renin and angiotensin Ⅱ were detected by ELISA. The mRNA and protein levels of ATF2

pATF2

MAFbx and MuRFl were detected by real-time PCR and Western blotting.       Results      Compared with the CC group

the weight of mouse body and gastrocnemius muscle were both increased in the CP group and CT group (P0.05)

which were still lower than that of the HC group (P0.05). The tumor mass and volume of the CT group were greater than that of the CP group

less than that of the CC group (P0.05). Compared with the CC group

the levels of renin and angiotensin Ⅱ in the serum and the mRNA and protein expression of ATF2

MuRFl and MAFbx in gastrocnemius muscle of the CP and CT group were decreased

however

the ratio of pATF2 to ATF2 were increased. The above results had statistical significance between the CP group and the CT group (P0.05).        Conclusion      CFZ ameliorates skeletal muscle consumption in cancer cachexia mice

which may be related to the inhibition of pATF2 degradation resulting in synthesis block of renin-angiotensin system and the suppression of ubiquitin proteasome pathway and tumor growth.